Micro-cuvette unit for facilitating the identification of samples

ABSTRACT

There is disclosed a micro-cuvette unit comprising a plurality of components in the form of a matrix which is arranged so that the cuvettes may be handled as one unit. The structural body of the micro-cuvette unit comprises a rectangular frame which is designed so that a plurality of cuvette components may be fitted to the frame, one after another. Each cuvette component comprises a plurality of cuvettes arranged in the form of a line or matrix and connected to each other directly or by means of support discs. The frame part of the micro-cuvette unit is open in the middle, at least within the area covered by the cuvettes in the cuvette components. The frame part contains two opposite sides which are provided with connecting means for joining the cuvette components to the frame part. These connecting means are different on different sides of the frame part and on different sides of the cuvette components so that their positions in relationship to each other may be readily determined and so that the identification of samples may be facilitated.

The subject of the present invention is a micro-cuvette unit thatcomprises several cuvettes in the form of a matrix as arranged so thatthey can be handled as one entire unit.

The micro-cuvette unit subject of the present invention can be used,e.g., for immunoassays, such as enzymeimmunoassay (EIA),hemagglutination (HA), hemagglutination inhibition (HI), complementfixation (CF), viroimmunoassay, and fluoroimmunoassay. Moreover, theunit is suitable for use in techniques and methods in which immobilizedenzymes are used, as such or as combined with other methods.

Enzymeimmunoassays (EIA, ELISA, and EMIT) have replaced, e.g,radioimmunoassay methods because they are mostly sufficiently specificand sensitive for many assays. The equipment needed for them isrelatively inexpensive, and mostly already existing in laboratories. Thereagents are inexpensive and their storage stability is good, thehandling procedures are simple, the assays rapid, and they permitautomation, and therein no isotopes or isotope counters are needed.

EIA, ELISA, and EMIT are suitable for the assay of antigens, antibodies,and haptenes.

As markers are used enzymes, such as alkaline phosphatase, peroxydase,glucose-oxydase, glucose-6-phosphate-hydrogenase, etc. The antigen,antibody, and haptene enzyme conjugate needed in these assays is stableand has a long storage age.

All the EIA types (competitive EIA on antigen, immunoenzymometric assayon antigen, sandwich EIA on antigen, EIA on antibody) except homogeneousEIA (EMIT) require a process by means of which it is possible toseparate fixed or free conjugate. For separation, the so-called solidphase is used to which the antigen or antibody is attached.

The microtiter plate is use is a plate of 8×12 matrix, in which thecuvettes are usually marked in the direction of 8 on the matrix from theright to the left from a to hand in the direction of 12 from 1 to 12.The microtiter plates of ×12 matrix comprise mainly three types ofcuvettes: U-bottom, V-bottom and flat bottom. For the flat bottomcuvettes the abbreviation FB is used, meaning flat bottom. The mostcommon registered microtiter plates are Cooke, Linbro, and Nunc.

Such a conventional microtiter plate is traditionally intended for HA(i.e. hemagglutination) and CF (i.e. complement fixation) techniques. Amore recent form of use is cell and tissue culture on microtiter platesspecifically treated for this purpose.

The uniformity of quality of conventional microtiter plates is so poorthat it causes excessive variation in enzyme-immunotests. Use of theplates in optical reading by means of a photometer suitable for thepurpose is unreliable, because the plates concerned do not meet therequirements of optical reading: the cuvette bottoms in the plates aresubjected to scratches and dirt, and mostly they are already scratchedbefore they are even taken to use.

Moreover, conventional microtiter plates vary from manufacturer tomanufacturer in respect of their outer dimensions, as do the plates ofthe same manufacturer also vary in respect of their size and uniformityof quality from production batch to production bath.

Conventional microtiter plates are too large (i.e. too many cuvettes perplate). As a rule, small matrixes are needed, because the number ofsamples is at one time not sufficient for efficient utilisation of theentire plate. On the other hand, it should be noticed that conventionalmicrotiter plates have an all too large quantity of rawmaterial per onecuvette.

A photometer of the type of vertical measurement and of high precisiondefinitely requires an FB-type shape of cuvette bottom in order thatoptical reading may be done reliably. Moreover, the bottom window of thecuvette must definitely meet the level required by optical reading, i.e.uniformity of quality, the window's remaining uncontaminated,unscratched, and free from finger-print contamination.

The micro-cuvette unit in accordance with the invention is mainlycharacterized in that the structural body of the micro-cuvette unitconsists preferably of a rectangular frame part, which is designed sothat two or more cuvette components can be fitted to the frame one afterthe other, each cuvette component consisting of several cuvettesarranged in the form of line or matrix and connected to each otherdirectly or by means of support discs and that the frame part of themicro-cuvette unit is open in the middle at least within the areacovered by the cuvettes in the cuvette components.

The invention is described more fully the following description and fromthe attached drawings, wherein

FIG. 1 shows the frame part of a micro-cuvette unit in accordance withthe invention as a side view and partly in section,

FIG. 2 shows the frame part of the micro-cuvette unit as viewed fromabove,

FIG. 3 shows a cuvette component intended for use with the frame part ofa micro-cuvette unit, as a schematical presentation viewed from above,

FIG. 4 shows a sectional perspective view of one cuvette in the cuvettecomponent of FIG. 3, and

FIG. 5 shows a construction embodiment alternative to the embodimentshown in FIG. 4, wherein two cuvettes are shown as a sectional sideview.

The micro-cuvette unit in accordance with the invention consists ofseveral parts. It comprises a rectangular frame part, whose middle part5 is open and into which smaller units can be placed and which smallerunits can be packed into this frame part 1 one after the other in line.The size of the frame part 1 is such that it suitable for being measuredin a photometer. The cuvette component 2 involves the advantage oflittle quantity of rawmaterial per cuvette 4. The matrix size of thecuvette component 2 is smaller than 8×12=96, whereby it satisfiesconsiderably more users.

Thus, the number of cuvettes 4 in the cuvette components 2 is less than96, e.g. 4×8=32 or 6×8=48 cuvettes.

Two or more cuvette components 2 have been arranged for attachment tothe frame part one after the other in line, each cuvette component 2consisting of several cuvettes 4 in line or matrix form, said cuvettesbeing connected to each other by means of support discs 3.

The optical window 12 of each cuvette 4 is protected by a collar 13,whereby said window's 12 becoming scratched, dirty, or contaminated byfinger prints is avoided. Moreover, it should be emphasized that it isconsiderably easier to manufacture cuvettes of optically higher standardif the cuvette-component matrix is smaller than 8×12, e.g. exactly 4×8cuvettes. Study results support this opinion, for, e.g., the FP-9cuvette component (matrix 3×3) is optically homogeneous. Moreover, ithas been noticed that the passive fixation of proteins is heterogeneous(from cuvette to cuvette) in a conventional microtiter plate of matrix8×12, wherein in a FP-9 cuvette component of matrix 3×3 this problem hasnot been noticed at all, but, on the contrary, the fixation is highlyhomogeneous from cuvette to cuvette in the same cuvette component and,moreover, from cuvette component to another cuvette component. Images ofscanning-electron microscope also speak in favour of homogeneity of 3×3FP-9 cuvette component, both as untreated (bare plastics surface) and,e.g., as coated with protein (antigen or antibody) or with any otherantigen. From ordinary microtitier plates (8×12=96) it has been noticedthat there are clear differences in charge between the middle areas andborder areas in the plate, which may be exactly the reason forheterogeneous passive absorption on the plastics surface.

FIG. 1 shows the frame part 1 of the micro-cuvette unit as a side view.In FIG. 1, the place for the cuvette component 2 is seen as a recess 9in the frame part 1. Moreover, e.g. in the way shown in the FIG. G., itis also possible to provide the recess 9 with a space 14 which makes iteasier to raise the cuvette component 2 from, and to lower it into, theframe part 1.

In FIG. 2, the frame part 1 is shown from above, whereby it is possibleto see the places for cuvette components 2, like from FIG. 1. The numberof these places may be, e.g., 3, in which case the matrix size is 4×8.The number of places may equally well be 2, in which case, on the otherhand, the matrix size is 6×8, or any other number whatsoever. Theindividual cuvette components 2 may be provided with separate codes eachof them, e.g., readable mechanically and/or visually.

FIG. 3 shows a cuvette component of 4×8 matrix. From the Figure it ispossible to see the narrower portions 10, 11 of different widths atdifferent ends of the cuvette component 2, constituting indication ofpolarity of the cuvette component 2. This indicator of polarity makes iteasier to identify the samples and, moreover, samples becomingintermixed with each other is prevented.

FIG. 4 is a sectional view of one cuvette 4 in a cuvette component 2.Each cuvette 4 is, around the optical window 12, provided with a collar13, whose object is to protect said window.

The collar 13 protecting the optical window 12 may limit the opticalwindow so as to be narrower than the diameter of the cuvette 4 bottom,in which case the optical window 12 is better protected from scratchesand finger prints and, moreover, the collar 13 in this way formedrestricts the diffused light from the light guide (e.g., fibre bundle).

FIG. 5 shows an embodiment alternative to that shown in FIG. 4, wherebythe same numerals as provided with an apostrophe are used forcorresponding parts. In this embodiment the cuvettes 4' are providedwith a square cross-sectional form, and two adjoining cuvettes have acuvette wall common for both of them. Of course, adjoining cuvettes witha common wall structure or part of same may also have othercross-sectional form except square.

According to a preferred method of manufacture, the cuvette componentsare manufactured as one piece out of plastics material so that theplastics material of the cuvette components 2 is non-transparent to themeasurement light with the exception of the optical windows 12 in thebottom portions of the cuvettes 4.

What we claim is:
 1. A micro-cuvette unit comprising a plurality ofcuvettes in the form of .[.a matrix arranged.]. .Iadd.rectangularlyshaped cuvette components .Iaddend.so that said cuvettes may be handledas .[.one unit.]. .Iadd.a unit, .Iaddend.wherein the structural body ofthe micro-cuvette unit comprises a rectangular frame part .Iadd.having arectangular opening .Iaddend.which is designed so that a plurality of.Iadd.rectangular .Iaddend.cuvette components may be fitted .[.to.]..Iadd.into .Iaddend.said frame one after the other, each.Iadd.rectangular .Iaddend.cuvette component comprising a plurality ofcuvettes arranged in the form of a line or matrix and connected to eachother directly or by means of .[.sufficient discs whereby.]..Iadd.support discs, .Iaddend.said .Iadd.rectangular opening of said.Iaddend.frame part .[.is.]. .Iadd.being .Iaddend.open in the middle.Iadd.thereof .Iaddend.at least within the area covered by said cuvettesin said .Iadd.rectangular .Iaddend.cuvette .[.components and.]..Iadd.components, .Iaddend.wherein said .Iadd.rectangular .Iaddend.framepart contains two opposite sides which are provided with connectingmeans for joining said cuvette components to said frame .[.part.]..Iadd.part, and .Iaddend.wherein said connecting means between saidframe part and said cuvette components are different on different sidesof said frame part and on different sides of said cuvette componentsrespectively so as to determine the positions of said cuvette componentsin relation to each other and to facilitate the identification ofsamples placed within said cuvettes and preventing said samples frombecoming intermixed with one another.
 2. The micro-cuvette unit of claim1 wherein said unit comprises several cuvettes in the form of a matrixarranged so that they may be handled as one unit, said micro-cuvetteunit comprising a rectangular frame part, designed so that two or morecuvette components may be fitted to said frame one after the other, eachcuvette component comprising a plurality of cuvettes which each containat lest one optical window in its bottom portion, said cuvette beingmade of a plastic material which is non-transparent to light measurementexcept through said optical window.
 3. The micro-cuvette unit of claim 1wherein each cuvette of said cuvette component comprises an opticalwindow in the bottom of said cuvette, said window being protectedunderneath by a collar that requires said optical window to be narrowerthan the diameter of said cuvette bottom on order to protect saidoptical window from scratches and fingerprints and to restrict thediffusion of light. .Iadd.
 4. The micro-cuvette unit as described inclaim 1, wherein said connecting means comprise said support discs onthe edges of said cuvette components and recesses on said frame forreceiving said support discs. .Iaddend. .Iadd.5. The micro-cuvette unitas described in claim 4, wherein said recesses are provided withopenings to facilitate lowering or raising said cuvette components intoor out of said frame. .Iaddend. .Iadd.6. The micro-cuvette unit asdescribed in claim 1, wherein each cuvette unit has a separate readablecode whereby identification of each cuvette unit is facilitated..Iaddend. .Iadd.7. The micro-cuvette as described in claim 1, whereinsaid rectangular cuvette component comprises a matrix of cuvettes..Iaddend. .Iadd.8. The micro-cuvette unit as described in claim 1,wherein said rectangularly shaped cuvette component is comprised of aplurality of cuvettes arranged in a line. .Iaddend. .Iadd.9. Themicro-cuvette unit as described in claim 1, wherein each cuvette iscoated with protein. .Iaddend.